Positron emission tomography (PET) is a non-invasive imaging technique that uses radioactive isotopes to map chemical or metabolic activity in living organisms. PET is commonly used to diagnose and monitor cancers, brain disorders and disease. It has also been an important research tool for investigating chemical and functional processes in the areas of biochemistry, biology, physiology, anatomy, molecular biology, and pharmacology. While traditional radiography and three dimensional imaging techniques, such as x-ray computed tomography (CT) and magnetic resonance imaging (MRI), provide structural information, PET scanning provides physiological information of metabolic activity leading to biochemical changes that generally occur long before the associated structural changes can be detected by the more traditional imaging techniques.
Positrons are positively charged electrons emitted by the nucleus of an unstable radioisotope. The radioisotope is unstable because it is positively charged and has too many protons. Release of the positron stabilizes the radioisotope by converting a proton into a neutron. For radioisotopes used in PET, the element formed from positron decay is stable. All radioisotopes used in PET decay by positron emission. The positron travels a small distance, which depends on its energy, before combining with an electron during a so-called “annihilation”. The annihilation of the positron and electron converts the combined mass into two gamma rays that are emitted at 180° to each other along a so-called “line of coincidence”. These gamma rays are readily detectable outside the human body by the detectors of the tomograph. The coincidence lines provide a detection scheme for forming the tomographic image.
Several radioisotopes are commonly used for PET including 11C, 18F, 15O, and 13N. The radioactive isotope that becomes a source of gamma rays for PET is first chemically incorporated into a compound forming a “tracer” of chemical or metabolic activity, which is then administered to the patient, typically by injection or inhalation. Compounds naturally occurring in the body are most useful for monitoring metabolic activity. Such compounds include glucose, oxygen, water, nitrogen, or ammonia. One common use of PET is to pinpoint which areas of the brain are used to perform a particular function. The technique uses a naturally occurring compound as a radioactive tracer. For example, when a subject is injected with a form of radioactive glucose, the glucose is delivered to the brain through the bloodstream. Since glucose normally fuels brain activity, the more active a part of the brain is during some experimental task, the more glucose it uses and the higher concentration of glucose in that part of the brain is revealed in the generated PET image.
Pharmaceutical drugs can also be tagged and administered, so that the drug itself is used as a tracer to determine the pharmacokinetics of its interactions in the brain or other body sites. PET scans can then provide in vivo repeated static measurements at a given time interval, or even dynamic measurements of the efficiency and distribution of the drug over time. Such measurements have been extremely useful to quantify the performance of a drug using a noninvasive technique. Such studies are becoming a more routine portion of testing used in the development of new, particularly psycho-active, pharmaceuticals.
Analogously, the phenomena of drug addiction has also been studied using PET. For example, PET images of drug addicts are compared with those of normal subjects. Such studies may make use of tagged neurotransmitters to examine the changes in receptor densities (numbers) or receptor binding affinities that result from long-term drug abuse.
Like other clinical imaging scanners, the typical PET scanner consists of detectors surrounding the subject to be imaged. The detectors are coupled to a scintillator, which converts gamma rays to light photons. The light photons are then converted into electrical impulses. Each electrical impulse generated at a detector corresponds to an “event”, or the arrival at the detector of a gamma-ray photon that originated at an annihilation within the subject.
Common prior art scintillator materials for gamma-ray detection include sodium iodide crystal, bismuth germinate (BGO), and barium fluoride (BaF2). The common prior art detectors include photomultiplier tubes.
The simultaneous or “coincident detection” of a pair of annihilation gamma rays by two detectors locates the line of coincidence along which an annihilation occurred due to chemical activity in the body. The detectors communicate with a central processing unit (CPU), at which a tomographic reconstruction technique is applied to generate or “reconstruct” a spatial mapping of the chemical activity in the body from a superposition of multiple lines of coincidence obtained from the entire array of detectors. Reconstruction of images from tomography data, using techniques such as filtered back-projection, is well known in the art and is described, for example, in A. C. Kak and M. Slaney, Principles of Computerized Tomographic Imaging, IEEE Press (1988), which is incorporated herein by reference.
In a typical PET scanner, each detector communicates with the CPU via independent data links, each of which is dedicated to a particular channel. The detector area commonly limits the spatial resolution obtainable in the reconstructed tomographic image. Therefore, to obtain good spatial resolution, it is not unusual for a PET scanner to be comprised of thousands of detectors with an equally large number of corresponding channels and data links.
One area of research that has benefited tremendously from the use of PET technology is medical research on the effects of pharmaceuticals in treating various diseases, cancers and drug addictions. For most of these types of studies, animal models must be used in place of human subjects, for obvious ethical reasons. PET imaging of animals, however, poses some problems. For example, in order to eliminate motion-induced artifacts from the PET image, it is necessary to immobilize the animal using an anesthetic. Unfortunately, anesthesia profoundly disturbs the neurological state of the animal, complicating the interpretation of PET results. The present state of the art PET scanners and methods of using PET have not addressed the problem of how to perform positron emission tomography on a conscious and awake animal or how to perform positron emission tomography on an awake animal while the animal performs some task.
In addition, human patients whose health management may benefit from the information provided by a PET scan are not always compliant with the requirement for maintaining a fixed position. Non-compliance may arise as a result of the very disease indication for which the PET scan results could usefully address, e.g. Parkinson's patients. Non-compliance may also arise in patients that are unable to understand the necessity of remaining in a fixed position, such as in children and/or the mentally disabled. The present state of the art PET scanners and methods of using PET have also not addressed the problem of how to perform positron emission tomography in human patients that are unable to maintain a fixed position, i.e., in a moving subject.
Moreover, although PET provides advanced functional information with a very high sensitivity, a major problem in PET imaging is the lack of anatomical information. Even dedicated animal PET scanners with a spatial resolution of 1 mm in the reconstructed image do not provide sufficient morphological structure, especially in applications with novel, very specific tracers or cell trafficking studies. Thus, in clinical applications, PET scanners are often combined with x-ray computed tomography (CT) to provide anatomical and functional information at the same time. While CT provides excellent contrast for bone structures, magnetic resonance imaging (MRI) yields excellent soft tissue contrast. Therefore, it would be desirable to combine the diagnostic benefits of a PET scanner with those of an MRI scanner.
There are many reasons for combining the functional information from PET with the anatomical (MRI), functional (fMRI) and spectroscopic (MRS) images that can be obtained with MR systems. For example, exploring relationships between structure and function by simultaneous mapping of PET and MR images, the ability to compare different brain mapping techniques such as fMRI and PET, accurate registration of PET and MR images, partial volume correction of PET data, temporal correlation of PET and MR spectroscopic images and motion correction of PET studies to permit imaging in conscious animals.
In addition, there are other, potentially more exciting possibilities for such a dual modality system. The validation of functional MRI (fMRI) techniques for brain mapping would be facilitated by the ability to perform fMRI and PET simultaneously in exactly the same imaging environment. Differences between the two methodologies, particularly in terms of precise spatial location of responses, could be investigated in the absence of image registration and scanning environment as confounding factors. The temporal correlation of PET and MR spectroscopic imaging or NMR spectroscopy could also be a very powerful tool for probing complex metabolic systems in vivo.
However, when combining different imaging modalities such as PET and MRI for the purpose of simultaneous imaging there are many issues that arise. For example, one major challenge is to develop PET detectors which can be used in a high magnetic field environment, to avoid susceptibility artifacts in the MR data due to the presence of the PET system and to eliminate electromagnetic interference effects between the PET and MR systems which could cause artifacts in either modality. Therefore, it is necessary to develop a PET detector which can operate without performance degradation in magnetic fields of several Tesla and which does not cause any noticeable distortion or artifacts in the MR images. Technical difficulties include avoiding the use of conducting or ferromagnetic materials in the PET detector front end, maintaining the homogeneity of the main magnetic field and minimizing electromagnetic interference (EMI) between PET and MR signals.
This is not a trivial task because all photon detectors and associated electronics contain metal components and their performance is usually very sensitive to magnetic fields and electromagnetic signals. In addition there are a number of practical issues. The PET system must be compact to fit inside the relatively narrow bore of most MR systems, it must be easy to take in and out of the MR scanner and it must be accurately located relative to the MR system to permit direct image registration. The cost of the system must also be a consideration for a practical device.
Unfortunately, photomultiplier tubes (PMTs) and their associated electronics used for scintillation light detection of conventional PET detectors do not work in such high magnetic fields. Accordingly, previous attempts to combine PET/MRI scanners involved using long optical fibers to transmit the light emitted from the scintillation crystals to PMTs located well outside the magnetic field associated with the MRI magnet. However, the long optical fibers transmit only a fraction (typically 20% or less) of the light produced in the scintillating crystals, which greatly reduces the energy resolution of the device. This results in large background levels and severely limits the type of physiological data that can be extracted.
Recent advances in solid-state electronics have opened the possibility of replacing PMTs with avalanche photodiode (APD) arrays that work well in high magnetic fields. For example, Pichler et al., in Performance Test of a LSO-APD PET Module in a 9.4 Tesla Magnet, IEEE Press (1998) and Development and Evaluation of a LSO-APD Block-Detector For Simultaneous PET-MR Imaging, IEEE Press (2004), have proposed a combined PET/MRI scanner utilizing APDs in place of PMTs. Here too, however, some of the front-end electronics of the proposed device are located outside of the magnetic field requiring electrical connection via relatively long coaxial cables which results in an increase in signal noise and distortion. Thus, the challenge remains in providing a compact device that can send the signals generated by the detectors and their associated electronics to the data acquisition equipment with minimal noise and distortion.
Accordingly, it would be desirable to provide a PET scanner combined with an MRI scanner that is not detrimentally affected by the magnetic fields produced by the MRI scanner.